The evolutionary ecology of methylation-dependent bacterial defense systems

Mobile genetic elements (MGEs) are central to microbial evolution, acting both as vectors of host genomic innovation by transferring adaptive genes between lineages, and as parasites, infection by which has driven the evolution of diverse host defense systems. Although recent years have seen a rapid expansion in defense system discovery, there remain considerable gaps in our understanding of the evolutionary ecology of MGEs and host defenses. Given the role of MGEs in spreading drug resistance alleles, the current focus on developing bacteriophages as alternative antimicrobials, and the ability for host defenses to interfere with both, it is essential to more fully understand these eco-evolutionary dynamics. As these dynamics are likely to be defense class specific, we focus initially on restriction modification systems, which are both ubiquitous and confer broad resistance, making them highly important in host-MGE coevolution. Firstly, using flow cytometry and high-throughput competition and coevolution experiments we demonstrate trade-offs between RM efficacy and fitness costs, as well as phage-mediated frequency dependent selection, that together provide insight into the maintenance of the high RM diversity observed in nature. Next, through experimentation we show that population-level RM diversity improves phage resistance, and through bioinformatics and mathematical modelling, how it can regulate horizontal gene transfer. These models also reveal how eco-evolutionary feedbacks can lead to counterintuitive positive associations between RM and MGEs. Finally, we move beyond RM to explore a novel methylation-dependent defense system. Using a large panel of sequenced phages we show that, comparable to RM, it confers broad resistance dependent largely on putative target site presence. Furthermore, our finding that many phage genomes are depleted of these target sites hints at a past selective pressure exerted on these phages by this system. Together, our work here highlights the importance of synthesizing mechanistic and eco-evolutionary perspectives to more fully understand how bacterial defense systems and MGEs interplay to structure microbial communities and shape the evolutionary trajectories of both host and MGE.<p></p>

Author dc:creator

• Joe Westley (21052958)

• Microbiology
• Ecology
• Evolution
• Bacterial defence systems
• Bacterial defense systems
• Mobile genetic elements
• Horizontal gene transfer

Statement dc:rights

• All rights reserved
• Open Access after 2027-05-11

Identifier

10779/exe.32346801.v1

OAI identifier oai:identifier

oai:figshare.com:article/32346801